Under conditions of natural or contrived alterations of environmental pressure and gas composition, respiratory gases can sustain life or can induce dysfunction, permanent damage or death. Only a narrow range of pressures of oxygen itself is tolerated by living cells, between metabolic failure of hypoxia and metabolic poisoning by hyperoxia. The respiration of man adapts to prolonged exposure to reduced atmospheric and oxygen pressures, and can tolerate extreme respiratory gas densities of high ambient pressures. This program concerns the acute and adaptive effects induced in man and animals by decreased and increased oxygen pressures, with emphasis upon changes in respiratory regulation. It concerns the rate of development of dysfunction due to oxygen poisoning, in cellular and integrated functions of the brain, as well as in the lungs, in each case with emphasis upon means of reducing toxicity and extending useful tolerance to oxygen for therapeutic and undersea applications. The Program involves adverse effects of inert respiratory gases, expressed as the gas lesion diseases of decompression sickness and isobaric inert gas counterdiffusion. Finally it concerns the interrelations of these effects of the respiratory gases in deep undersea activity and in therapy.